Mitochondrial ATP formation

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Inside the Mitochondrion

• Mitochondrion is the site of eukaryotic oxidative phosphorylation.

• It contains enzymes such as pyruvate dehydrogenase, the citric acid cycle enzymes, the enzymes catalyzing fatty acid oxidation, and the enzymes and redox proteins involved in electron transport and oxidative phosporylation.

• Mitochondrial generated reaches the cytosol, whereas ADP and Pi from the cytosol enter the mitochondria. Pi enters the mitochondria using phosphate carrier. Ca2+ (required by ATP synthase) is absorbed and released by the mitochondria using pumps.

• The equation for ATP generation carried out with the help of the citric acid cycle is: ADP + Pi + H+ ----> ATP + H2O 7.3 kcal mol-1 ; 30.5 kJ mol-1, Accomplished by ATP synthase, complex V (proton-translocating ATP synthase), driven by the electron-transport process; originally discovered as an ATPase acting in the reverse direction.

What is Oxidative Phosphorylation?

• The coupling of the standard free energy of oxidation of NADH and ATP synthesis is called oxidative phosphorylation. Oxidation of 1 NADH = 3 ATP. Under standard conditions the energy coupled is ~70% efficient. Compare that to the ~30% efficiency of an automobile engine.

• Oxidation and phosphorylation are closely coupled in well functioned mitochondria, so electron transport can occur only if ADP is being phosphorylated.

• The synthesis of ATP from ADP and Pi in mitochondria is catalyzed by proton-translocating ATP synthase (Complex V), and is driven by the electron transport process.

• Since electron transport and oxidative phosphorylation are coupled, electron transport does not occur unless ADP is present. The level of ADP is the most important factor in determining ATP synthesis. Of course, Pi, O2, and NADH are needed.

Types of oxidation of NADH - ATP synthesis coupling:

Chemical coupling:

Says that electron transport yielded reactive intermediates whose subsequent breakdown drove oxidative phosphorylation.

Conformational coupling:

Says that electron transport causes proteins of the inner mitochondrial membrane to assume activated of energized conformational states, which are somehow associated with ATP synthase.

Chemiosmotic coupling:

Says the free energy of electron transport is conserved by pumping H+ from the mitochondrial matrix to the intermembrane space so as to create an electrochemical H+ gradient across the inner mitochondrial membrane. The electrochemical potential of this gradient is harassed to generate ATP. So far, this theory is widely accepted.

Mitochondrial ATP Formation:

Mitochondrial ATP formation

ATP Synthase Structure:

• The ATP synthase is a multisubunit transmembrane protein.

• It consists of two major substructures comprising 8 - 13 different subunits.

• There are two main functional subunits: F0 and F1.

• F0 is a water soluble transmembrane protein composed of up to 8 subunits. F1 is a water soluble peripheral protein composed of five types of subunits.

• F1F0 are dumbbell shaped, and are joined by a 45 Armstrong long central stalk and a less substantial peripherally located connector.

Mitochondria and Aging:

Mitochondrial efficiency decrease with age.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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